Formation of a new carbon—carbon bond at a position α to an electron withdrawing group, i.e. at an activated methyl, methylene or methine carbon, is typically achieved by nucleophilic attack of the conjugate base of the activated carbon, e.g., an enolate or ketene acetal, at an electrophilic carbon, e.g., a carbonyl carbon or a carbon bearing a good leaving group. While this paradigm is effective in a range of contexts, e.g., the aldol condensation and enolate alkylation, its scope, in fact, is limited. For example, existing methods for the formation of a carbon—carbon bond between an sp2-hybridized carbon of an aromatic nucleus and an activated carbon require that the aromatic nucleus be susceptible to nucleophilic aromatic substitution, e.g., that it bear a number of electron withdrawing groups in appropriate positions. Furthermore, corresponding limitations exist in the art vis-a-vis the ability to install a vinyl group at an activated carbon, i.e. the requirement that the vinylating group be predisposed to an addition-elimination mechanism. A general method for the arylation and/or vinylation of activated methyl, methylene, and methine carbons, that utilizes readily available starting materials and affords products in high regioselectivity, is not known in the art.
The synthesis of α-aryl ketones has received much attention over the past two decades. A number of stoichiometric arylating reagents have been successfully developed for this purpose, however, their utility is decreased because each synthesis of an α-aryl ketone requires the synthesis of a different arylating reagent. In contrast, the direct coupling of aryl halides with ketones would provide a convenient method for the synthesis of α-aryl ketones. Semmelhack et al. have demonstrated that Ni(COD)2 catalyzes the intramolecular coupling of an aryl iodide with a ketone enolate. While there are reports of Pd or Ni-catalyzed intermolecular coupling reactions that afford α-aryl ketones, these methods require the use of stoichiometric amounts of tin reagents, and/or the use of enol ether, enamine or α-chloroketone derivatives instead of the ketone. Thus, a general method which utilizes readily available starting materials and affords products in high regioselectivity has not been realized.